Lipid vesicles have unilamellar or multilamellar exterior walls that enclose an internal space. The walls of lipid vesicles are bimolecular layers (bilayers) of one or more polar lipid components having polar heads and non-polar tails. In an aqueous liquid, or other polar liquid, the polar heads of one layer may orient outwardly to extend into the surrounding medium, the non-polar tail portions of the lipids thus associating with each other. This orientation provides a layer having a polar surface on either side of the layer, and having a non-polar core between the surfaces. In a lipid vesicle, the bilayer forms a closed structure, where both the exterior and the interior of the structure have a polar surface. Unilamellar vesicles have one such bilayer, whereas multilamellar vesicles typically have multiple, concentric bilayers.
One application of lipid vesicles is in the delivery of bioactive agents within an organism. Examples of bioactive agents include drug agents and imaging agents. Lipid vesicles may be used to isolate a bioactive agent, so as to direct the agent away from certain tissues and to deliver the agent to other tissues. Lipid vesicles also can be used to release drugs over a prolonged period of time, allowing for less frequent administration. In addition, lipid vesicles can allow for delivery of hydrophobic or amphiphilic drugs that would otherwise be difficult to administer by injection.
In one example of bioactive agent delivery, lipid vesicles have been researched for use with chemotherapeutic agents. Tumor-specific drug delivery has become an important area of research in cancer therapy. Application of chemotherapeutics for cancer treatment is often limited by severe side effects and poor systemic efficacy. Lipid vesicle delivery systems have decreased these pharmacokinetic drawbacks, resulting in a number of delivery systems for cancer treatment that have been approved by the U.S. Food & Drug Administration (FDA). These approved liposome delivery systems, however, release the encapsulated agent through passive diffusion from the vesicle or through slow, non-specific degradation of the vesicle. These mechanisms can lead to systemic toxicity and also lack the ability to actively release the encapsulated agent at a specific disease site and/or at a specific time.
At present, most lipid vesicle mediated bioactive agent delivery is either untargeted or passively targeted. Passive targeting involves stabilizing the lipid vesicle against degradation in the circulatory system, providing for an increase in blood circulation times. A typical approach to this stabilization is to coat the lipid vesicle with a hydrophilic polymer, such as poly(ethylene glycol) (PEG). A common drawback to the untargeted or passively targeted strategies is the lack of accuracy in delivering the bioactive agent to a specific tissue type or a specific area of the organism.
It would be desirable to provide a lipid vesicle system in which the contents of the vesicle are released when the vesicle is in contact with a specific environment, such as a specific type of tissue within an organism. Preferably, such a system would protect the vesicle contents until contacted with an agent that is present specifically at the targeted environment, at which point the contents would be released. For biological applications, it would be desirable for the vesicle contents to be released when the vesicle is in contact with a biomarker specific for the targeted tissue.